-Herbal Medicine, Healing, and Cancer :..Herbal Medicine, Healing and Cancer is for humans but the information within
it is so awesome and it contains preventative tips also. Donald Yance has
reviewed the literature and has treated human cancer victims for over twenty
years..amazon sells it for less than $16 dollars! For instance, I almost bought
Melatonin for Yuki who just had radical surgery in case of mammary
cancer(thank goodness it was a cyst) because of that book. I wish I had known
about two years ago when I started the search to keep Morgan alive. He also
explains why possibly flaxseed and cottage cheese may work-He explains what
butryic acid is.

Here is his excerpt on flaxseed oil and sulphur rich protein

Herbal Medicine, Healing &
Cancer" by Donald Yance"Flaxseed oil is rich in essential fatty acids, particularly ALA, which,
when taken in combination with sulfur-rich proteins, actually works to
create a new food. This was first discovered and made famous by Johanna
Budwig, a West German physician who had done a great deal of research on the
oil-protein combination. She discovered that EFAs need to bind to
sulfur-rich proteins (she used low-fat cottage cheese) before the body can
properly assimilate them. Budwig found that by feeding people with terminal
cancer this oil-protein combination, the yellowish-green substance in their
blood was replaced by the healthy red pigment, hemaglobin. The phosphatides
returned and the lipoproteins reappeared.Of all the deficiencies that may exist in people with cancer, perhaps those
that are most important and totally ignored are EFAs, which, when taken with
protein, enhance our albumin levels. Albumin is a blood protein of immense
importance to good health. When flaxseed oil and sulfur-rich protein are
combined, the ALA and the EFAs in the flaxseed oil become water-soluble and
electron-rich; this causes the cell membrane to become more stable by making
it more flexible and fluidlike. The electron-rich fatty acids now allow for
efficient transport of materials and energy between the inner and outer cell
membrane. This is important to the health of all cells and to the entire
immune system.A simple recipe for achieving these cellular benefits is to add 1 to 2
teaspoons of flaxseed oil or ground flaxseeds to 1 cup of organic yogurt
(preferabley goat or soy yogurt).Omega-3 fatty acids are extremely important because they modulate
prostaglandins, which are very active biological substances important to
nearly every bodily function. They suppress tumor-promoting prostaglandin E2
by increasing prostiglandin E3 and suppressing AA. They also inhibit cancer
wasting. EPA and ALA, as well as other related omega-3 fatty acids, plus GLA
from evening primrose oil, have been found to kill a number of tumor-cell
lines and cause a significant reduction in tumor growth in animal studies."
(pp.219-220)

Mutat Res. 2004 Jul 13;551(1-2):213-22. :
The influence of dietary flaxseed and other grains, fruits and vegetables on the frequency of spontaneous chromosomal damage in mice.
Trentin GA, Moody J, Torous DK, Thompson LU, Heddle JA.
Department of Biology, York University, 4700 Keele Street, Toronto, Ont., Canada M3J 1P3.
Spontaneous genetic damage, whether mutations or chromosomal aberrations, undoubtedly arise from a variety of sources including replication errors, oxidative damage, background radiation, and chemical exposure. Given the numerous correlations between diet and cancer, it seemed possible that diet could influence the spontaneous rate of DNA damage and its genetic consequences. Since diets high in vegetables, fruits, and grains are associated with lower rates of cancer, we supplemented the diets of mice and measured the frequency of micronuclei in the peripheral blood. Micronuclei arise from broken chromosomes or chromosome loss in the erythroblast. They are first seen in the short reticulocyte stage of the red blood cell but persist for the entire 30-day lifespan of the cell in mice. C57Bl mice were placed on a defined diet (AIN-93G) supplemented to 20% final dry weight with grains or freeze-dried fruits or vegetables. The micronucleus frequency was measured in a pre-exposure blood sample and every 2 weeks thereafter for 6 weeks. This was possible in spite of the low spontaneous frequency of 1/1000-2/1000 cells by the use of a novel flow cytometric method, which permitted the analysis of both the mature red blood cells and reticulocytes. Of the foods tested, flaxseed proved to be the most protective by reducing the incidence of micronuclei in both the reticulocyte and normochromatic erythrocyte cell populations by 30 and 11%, respectively. The results show that at least one class of spontaneous genetic damage can be modified by diet and suggests that short-term experiments with small numbers of animals can be used to identify dietary anticarcinogens that may influence human cancer rates.Urology. 2004 May;63(5):900-4. :
Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen.
Demark-Wahnefried W, Robertson CN, Walther PJ, Polascik TJ, Paulson DF, Vollmer RT.
Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth. Am J Clin Nutr. 2004 Feb;79(2):318-25. :
Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy.
Brooks JD, Ward WE, Lewis JE, Hilditch J, Nickell L, Wong E, Thompson LU.
Department of Nutritional Sciences, University of Toronto, Toronto, Canada.
BACKGROUND: Phytoestrogens, which are abundant in flaxseed and soy, have chemical structures resembling those of endogenous estrogens and have been shown to exert hormonal effects, thereby affecting chronic diseases. OBJECTIVE: We compared the effects of consuming equal amounts of flaxseed or soy on estrogen metabolism and biochemical markers of bone metabolism in postmenopausal women. DESIGN: In a parallel design, the diet of postmenopausal women (n = 46) was supplemented with either a placebo, soy (25 g soy flour), or flaxseed (25 g ground flaxseed) muffin for 16 wk. Blood and 24-h urine samples were collected at baseline and at the endpoint. Urine samples were analyzed for phytoestrogens, estrogen metabolites (2-hydroxyestrone, 16alpha-hydroxyestrone), and serum hormones (estradiol, estrone, estrone sulfate). Serum and urine samples were also analyzed for biochemical markers of bone metabolism. RESULTS: Urinary concentrations of 2-hydroxyestrone, but not of 16alpha-hydroxyestrone, increased significantly in the flaxseed group (P = 0.05). In the flaxseed group, the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone was positively correlated with urinary lignan excretion (r = 0.579, P = 0.02). In the soy and placebo groups, no significant correlation was observed. No significant change in serum hormones or biochemical markers of bone metabolism was observed within or between the treatment groups. CONCLUSIONS: Supplementation with flaxseed modifies urinary estrogen metabolite excretion to a greater extent than does supplementation with an equal amount of soy. This modification by flaxseed is associated with an increase in urinary lignan excretion. Despite the shift in estrogen metabolism to favor the less biologically active estrogens, a negative effect on bone cell metabolism was not observed.
Kidney Int. 2003 Dec;64(6):2100-2107. :
Dietary flaxseed meal reduces proteinuria and ameliorates nephropathy in an animal model of type II diabetes mellitus.
Velasquez MT, Bhathena SJ, Ranich T, Schwartz AM, Kardon DE, Ali AA, Haudenschild CC, Hansen CT.
Department of Medicine and Department of Pathology, George Washington University Medical Center, Washington D.C.; Phytonutrients Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland; Jerome Holland Laboratories, American Red Cross, Rockville, Maryland; and National Institutes of Health, Animal Genetic Resource, Bethesda, Maryland.
Background. Evidence is emerging that varying the type or source of dietary protein intake can have beneficial effects on chronic renal disease. Consumption of soybean and soy-based food products, as the source of plant protein, can retard the development and progression of chronic renal disease. We studied the obese spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat, a model of obesity and type II diabetes mellitus that consistently develops nephropathy resembling diabetic nephropathy. We specifically sought to determine whether changing the source of protein intake from animal protein, casein, to plant protein in the form of either soy protein concentrate or flaxseed protein in the diet has a different impact on renal function and nephropathy in this model. Methods. Male obese SHR/N-cp rats were randomly assigned to one of three diets containing either 20% casein, 20% soy protein concentrate, or 20% flaxseed meal. Except for the protein source, all three diets were identical and contained similar amounts of protein, fat, carbohydrates, minerals, and vitamins. All animals were maintained on these diets for 6 months. At the end of the study, blood sampling and 24-hour urine collections were performed for renal functional measurements, and the kidneys were harvested and examined for histologic evaluation. Results. All three groups had similar amounts of food intake and body weight gain and exhibited fasting hyperglycemia and hyperinsulinemia. Plasma glucose levels did not differ among the three groups, but plasma insulin concentration was significantly lower in rats fed flaxseed meal than those fed either casein or soy protein concentrate. Mean plasma creatinine, creatinine clearance, and urinary urea excretion also did not differ significantly between the three groups. By contrast, urinary protein excretion was significantly lower (P < 0.01) in rats fed flaxseed than in rats fed either casein or soy protein concentrate. Morphologic analysis of renal structural lesions showed that the percentage of abnormal glomeruli with mesangial expansion and the tubulointerstitial score (an index of severity of tubulointerstitial damage) were significantly reduced in rats fed flaxmeal compared to those fed casein or soy protein concentrate. Conclusion. We conclude that dietary protein substitution with flaxseed meal reduces proteinuria and glomerular and tubulointerstitial lesions in obese SHR/N-cp rats and that flaxseed meal is more effective than soy protein in reducing proteinuria and renal histologic abnormalities in this model. The reduction in proteinuria and renal injury was independent of the amount of protein intake and glycemic control. Which dietary component(s) present in flaxseed meal is (are) responsible for the renal protective effect remains to be determined.
: Am Fam Physician. 2004 Jul 1;70(1):133-40. :
Comment in:
Am Fam Physician. 2004 Jul 1;70(1):34-5.
Omega-3 fatty acids.
Covington MB.
University of Maryland School of Medicine, Center for Integrative Medicine, Baltimore, Maryland 21207, USA. mcovington@compmed.umm.edu
Omega-3 fatty acids have been shown to significantly reduce the risk for sudden death caused by cardiac arrhythmias and all-cause mortality in patients with known coronary heart disease. Fatty fish, such as salmon and tuna, and fish oil are rich sources of the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. Flaxseed, canola oil, and walnuts also are good dietary sources of omega-3 fatty acids. In addition to being antiarrhythmic, the omega-3 fatty acids are antithrombotic and anti-inflammatory. In contrast, omega-6 fatty acids, which are present in most seeds, vegetable oils, and meat, are prothrombotic and proinflammatory. Omega-3 fatty acids also are used to treat hyperlipidemia, hypertension, and rheumatoid arthritis. There are no significant drug interactions with omega-3 fatty acids. The American Heart Association recommends consumption of two servings of fish per week for persons with no history of coronary heart disease and at least one serving of fish daily for those with known coronary heart disease. Approximately 1 g per day of eicosapentaenoic acid plus docosahexaenoic acid is recommended for cardioprotection. Higher dosages of omega-3 fatty acids are required to reduce elevated triglyceride levels (2 to 4 g per day) and to reduce morning stiffness and the number of tender joints in patients with rheumatoid arthritis (at least 3 g per day). Modest decreases in blood pressure occur with significantly higher dosages of omega-3 fatty acids.
Gut. 2003 Oct;52(10):1479-86. :
Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial.
Fearon KC, Von Meyenfeldt MF, Moses AG, Van Geenen R, Roy A, Gouma DJ, Giacosa A, Van Gossum A, Bauer J, Barber MD, Aaronson NK, Voss AC, Tisdale MJ.
Royal Infirmary of Edinburgh, Edinburgh, UK.
AIM: N-3 fatty acids, especially eicosapentaenoic acid (EPA)[ie oil from cold water fish], may possess anticachectic properties. This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants (experimental: E) with an isocaloric isonitrogenous control supplement (C) for their effects on weight, lean body mass (LBM), dietary intake, and quality of life in cachectic patients with advanced pancreatic cancer. METHODS: A total of 200 patients (95 E; 105 C) were randomised to consume two cans/day of the E or C supplement (480 ml, 620 kcal, 32 g protein +/- 2.2 g EPA) for eight weeks in a multicentre, randomised, double blind trial. RESULTS: At enrolment, patients' mean rate of weight loss was 3.3 kg/month. Intake of the supplements (E or C) was below the recommended dose (2 cans/day) and averaged 1.4 cans/day. Over eight weeks, patients in both groups stopped losing weight (delta weight E: -0.25 kg/month versus C: -0.37 kg/month; p = 0.74) and LBM (Delta LBM E: +0.27 kg/month versus C: +0.12 kg/month; p = 0.88) to an equal degree (change from baseline E and C, p<0.001). In view of evident non-compliance in both E and C groups, correlation analyses were undertaken to examine for potential dose-response relationships. E patients demonstrated significant correlations between their supplement intake and weight gain (r = 0.50, p<0.001) and increase in LBM (r = 0.33, p = 0.036). Such correlations were not statistically significant in C patients. The relationship of supplement intake with change in LBM was significantly different between E and C patients (p = 0.043). Increased plasma EPA levels in the E group were associated with weight and LBM gain (r = 0.50, p<0.001; r = 0.51, p = 0.001). Weight gain was associated with improved quality of life (p<0.01) only in the E group. CONCLUSION: Intention to treat group comparisons indicated that at the mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were equally effective in arresting weight loss. Post hoc dose-response analysis suggests that if taken in sufficient quantity, only the n-3 fatty acid enriched energy and protein dense supplement results in net gain of weight, lean tissue, and improved quality of life. Further trials are required to examine the potential role of n-3 enriched supplements in the treatment of cancer cachexia.

Flaxseed inhibits metastasis and decreases extracellular vascular
endothelial growth factor in human breast cancer xenografts
Angiogenesis is important in tumor growth, progression and metastatic dissemination. Vascular
endothelial growth factor (VEGF) is one key factor in promotion of breast cancer angiogenesis.
VEGFs are bioactive in the extracellular space where they become available to the endothelial
cells. Phytoestrogens such as lignans have been shown to alter breast cancer incidence and be
cancer-protective in rats. We show that supplementation of 10% flaxseed, the richest source of
mammalian lignans, to nude mice with established human breast tumors reduced tumor growth and
metastasis. Moreover, flaxseed decreased extracellular levels of VEGF, which may be one
mechanistic explanation to the decreased tumor growth and metastasis J Nutr 2002 Nov;132(11 Suppl):3508S-3512S
:
Omega-3 fatty acids to augment cancer therapy.
Hardman WE.
Pennington Biomedical Research Center, Louisiana State University, Baton
Rouge, LA 70808, USA. hardmawe@pbrc.eduThe results of animal studies have demonstrated that the consumption of
omega-3 fatty acids can slow the growth of cancer xenografts, increase the
efficacy of chemotherapy and reduce the side effects of the chemotherapy or
of the cancer. Molecular mechanisms postulated to contribute to the multiple
benefits of omega-3 fatty acids include 1) suppressing the expression of
cyclooxygenase-2 in tumors, thus decreasing proliferation of cancer cells and
reducing angiogenesis in the tumor; 2) decreasing the expression of AP-1 and
ras, two oncogenes implicated in tumor promotion; 3) inducing differentiation of
cancer cells; 4) suppressing nuclear factor-kappaB activation and bcl-2
expression, thus allowing apoptosis of cancer cells; and 5) reducing
cancer-induced cachexia. It seems reasonable to assume that after appropriate
cancer therapy, consumption of omega-3 fatty acids might slow or stop the
growth of metastatic cancer cells, increase longevity of cancer patients and
improve their quality of life.Am J Med 2002 Dec 30;113 Suppl 9B:71-88
:
Bioactive compounds in foods: their role in the prevention of
cardiovascular disease and cancer.
Kris-Etherton PM, Hecker KD, Bonanome A, Coval SM, Binkoski AE, Hilpert
KF, Griel AE, Etherton TD.
Graduate Program in Nutrition, Pennsylvania State University, (PMK, KDH,
SMC, AEB, KFH, AEG, TDE), University Park, Pennsylvania, USA"Bioactive compounds" are extranutritional constituents that typically occur in
small quantities in foods. They are being intensively studied to evaluate their
effects on health. The impetus sparking this scientific inquiry was the result of
many epidemiologic studies that have shown protective effects of plant-based
diets on cardiovascular disease (CVD) and cancer. Many bioactive compounds
have been discovered. These compounds vary widely in chemical structure and
function and are grouped accordingly. Phenolic compounds, including their
subcategory, flavonoids, are present in all plants and have been studied
extensively in cereals, legumes, nuts, olive oil, vegetables, fruits, tea, and red
wine. Many phenolic compounds have antioxidant properties, and some studies
have demonstrated favorable effects on thrombosis and tumorogenesis and
promotion. Although some epidemiologic studies have reported protective
associations between flavonoids or other phenolics and CVD and cancer, other
studies have not found these associations. Various phytoestrogens are present in
soy, but also in flaxseed oil, whole grains, fruits, and vegetables. They have
antioxidant properties, and some studies demonstrated favorable effects on
other CVD risk factors, and in animal and cell culture models of cancer.
However, because phytoestrogens act both as partial estrogen agonists and
antagonists, their effects on cancer are likely complex. Hydroxytyrosol, one of
many phenolics in olives and olive oil, is a potent antioxidant. Resveratrol, found
in nuts and red wine, has antioxidant, antithrombotic, and anti-inflammatory
properties, and inhibits carcinogenesis. Lycopene, a potent antioxidant
carotenoid in tomatoes and other fruits, is thought to protect against prostate
and other cancers, and inhibits tumor cell growth in animals. Organosulfur
compounds in garlic and onions, isothiocyanates in cruciferous vegetables, and
monoterpenes in citrus fruits, cherries, and herbs have anticarcinogenic actions
in experimental models, as well as cardioprotective effects. In summary,
numerous bioactive compounds appear to have beneficial health effects. Much
scientific research needs to be conducted before we can begin to make
science-based dietary recommendations. Despite this, there is sufficient
evidence to recommend consuming food sources rich in bioactive compounds.
From a practical perspective, this translates to recommending a diet rich in a
variety of fruits, vegetables, whole grains, legumes, oils, and nuts.

Polyunsaturated fatty acids are potent neuroprotectors.
Lauritzen I, Blondeau N, Heurteaux C, Widmann C, Romey G, Lazdunski M.
Institut de Pharmacologie Moleculaire et Cellulaire, CNRS UPR 411, 660 route des Lucioles,
Sophia Antipolis, 06560 Valbonne, France.
Results reported in this work suggest a potential therapeutic value of polyunsaturated fatty acids
for cerebral pathologies as previously proposed by others for cardiac diseases. We show that the
polyunsaturated fatty acid linolenic acid prevents neuronal death in an animal model of transient
global ischemia even when administered after the insult. Linolenic acid also protects animals
treated with kainate against seizures and hippocampal lesions. The same effects have been
observed in an in vitro model of seizure-like activity using glutamatergic neurons and they have
been shown to be associated with blockade of glutamatergic transmission by low concentrations
of distinct polyunsaturated fatty acids. Our data suggest that the opening of background K(+)
channels, like TREK-1 and TRAAK, which are activated by arachidonic acid and other
polyunsaturated fatty acids such as docosahexaenoic acid and linolenic acid, is a significant factor
in this neuroprotective effect. These channels are abundant in the brain where they are located
both pre- and post-synaptically, and are insensitive to saturated fatty acids, which offer no
neuroprotection.Biosynthetic pathway to the cancer chemopreventive secoisolariciresinol
diglucoside-hydroxymethyl glutaryl ester-linked lignan oligomers in flax
(Linum usitatissimum) seed.Application of stable and radioisotope precursor/tracer experiments resulted in the identification
of various phenylpropanoid, monolignol, and lignan metabolites involved in the biosynthesis of the
cancer chemopreventive secoisolariciresinol diglucoside (SDG; 1)-containing ester-linked
"polymer(s)" in flax (Linum usitatissimum) seed. Results from this
study will facilitate future isolation and characterization of the proteins and enzymes involved in
biosynthesis of the SDG-HMG ester-linked oligomers in flax seed."1: Carcinogenesis 1996 Jun;17(6):1373-6 Flaxseed and its lignan and oil components reduce
mammary tumor
growth at a late stage of carcinogenesis. Thompson LU, Rickard SE, Orcheson LJ, Seidl MM. Department of Nutritional Sciences, Faculty of Medicine,
University of Toronto, Ontario,
Canada. Flaxseed, a rich source of mammalian lignan precursor
secoisolariciresinol-diglycoside (S.D.) and
alpha-linolenic acid (ALA), has been shown to be
protective at the early promotion stage of
carcinogenesis. The objective of this study was to
determine whether supplementation with
flaxseed, its lignan or oil fractions, beginning 13
weeks after carcinogen administration, would
reduce the size of established mammary tumors (present
at the start of treatment) and appearance
of new tumors in rats. Dietary groups consisted of the
basal diet (BD, 20% corn oil) alone or
supplemented with a gavage of 2200 nmol/day S.D. [S.D.,
equal to level in 5% flaxseed (F)],
1.82% flaxseed oil (OIL, equal to level in 5% F) or 2.5%
or 5% flaxseed (2.5% F and 5% F,
respectively). After 7 weeks of treatment, established
tumor volume was over 50% smaller in all
treatment groups (OIL, 2.5% F, 5% F, P < 0.04; S.D., P < 0.08) while there was no change in
the BD group. New tumor number and volume were lowest in
the S.D. (P < 0.02) and 2.5% F
(P < 0.07) groups. The combined established and new tumor volumes were smaller for
the S.D.,
2.5% F and 5% F groups (P < 0.02) compared to the OIL and BD groups. The high negative
correlation (r = -0.997, P < 0.001) between established tumor volume and urinary mammalian
lignan excretion in the BD, S.D., 2.5% F and 5% F groups
indicates that the reduction in tumor
size is due in part to the lignans derived from the S.D.
in flaxseed. However, there was no
relationship between new or total tumor development and
urinary lignan levels. The effect of
flaxseed oil may be related to its high ALA content. In
conclusion, the S.D. in flaxseed appears to
be beneficial throughout the promotional phase of
carcinogenesis whereas the oil component is
more effective at the stage when tumors have already
been established. Clin Cancer Res. 2003 Oct 15;9(13):4653-65. :
Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence.
Trikha M, Corringham R, Klein B, Rossi JF.
Centocor, Malvern, Pennsylvania 19355 [M. T., R. C.], and Unit of Cellular Therapy and INSERM U475 [B. K.] and Service d'Hematologie et d'Oncologie Medicale and INSERM U475 [J-F. R.], Montpellier, France 34295.

Interleukin (IL)-6, a pleiotropic cytokine with varied systemic functions, plays a major role in inflammatory processes. It modulates the transcription of several liver-specific genes during acute inflammatory states, particularly C-reactive protein, and controls the survival of normal plasmablastic cells. In addition, IL-6 has been implicated in hematopoiesis as a cofactor in stem cell amplification and differentiation. This article is the first review of clinical studies in the 1990s with anti-IL-6 monoclonal antibodies (mAbs) in the treatment of patients with cancer and related lymphoproliferative disorders. In six clinical studies of mAbs to IL-6 with BE-8 or CNTO 328 in patients with multiple myeloma, renal cell carcinoma, and B-lymphoproliferative disorders, anti-IL-6 mAb treatment decreased C-reactive protein levels in all patients. In most patients, levels decreased below detectable limits. The antibodies were well tolerated, and no serious adverse effects were observed in the vast majority of studies. The fact that anti-IL-6 mAb therapy decreased the incidence of cancer-related anorexia and cachexia may also be useful in the treatment of cancer patients Am J Clin Nutr. 2000 Jan;71(1 Suppl):343S-8S. :
Dietary polyunsaturated fatty acids and inflammatory mediator production.
James MJ, Gibson RA, Cleland LG.
Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia, and the Department of Pediatrics and Child Health, Flinders Medical Center, Bedford Park, Australia.
Many antiinflammatory pharmaceutical products inhibit the production of certain eicosanoids and cytokines and it is here that possibilities exist for therapies that incorporate n-3 and n-9 dietary fatty acids. The proinflammatory eicosanoids prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) are derived from the n-6 fatty acid arachidonic acid (AA), which is maintained at high cellular concentrations by the high n-6 and low n-3 polyunsaturated fatty acid content of the modern Western diet. Flaxseed oil contains the 18-carbon n-3 fatty acid alpha-linolenic acid, which can be converted after ingestion to the 20-carbon n-3 fatty acid eicosapentaenoic acid (EPA). Fish oils contain both 20- and 22-carbon n-3 fatty acids, EPA and docosahexaenoic acid. EPA can act as a competitive inhibitor of AA conversion to PGE(2) and LTB(4), and decreased synthesis of one or both of these eicosanoids has been observed after inclusion of flaxseed oil or fish oil in the diet. Analogous to the effect of n-3 fatty acids, inclusion of the 20-carbon n-9 fatty acid eicosatrienoic acid in the diet also results in decreased synthesis of LTB(4). Regarding the proinflammatory ctyokines, tumor necrosis factor alpha and interleukin 1beta, studies of healthy volunteers and rheumatoid arthritis patients have shown < or = 90% inhibition of cytokine production after dietary supplementation with fish oil. Use of flaxseed oil in domestic food preparation also reduced production of these cytokines. Novel antiinflammatory therapies can be developed that take advantage of positive interactions between the dietary fats and existing or newly developed pharmaceutical products.: Curr Opin Clin Nutr Metab Care 2003
Mar;6(2):195-201
:
Metabolic and nutritional support in acute cardiac failure.
Berger MM, Mustafa I.
Intensive Care Unit and Burns Centre, University Hospital, Lausanne,
Switzerland; and Intensive Care Unit, National Cardiac Center, Jakarta,
Indonesia.PURPOSE OF REVIEW Cardiovascular disease is one of the most important
causes of morbidity and mortality in western countries, generating an increasing
number of admissions to intensive care units. Cardiac failure has long been
associated with nutritional disorders, malnutrition and cachexia being frequent
during the late phases of congestive heart failure: undernutrition is also a
determinant of outcome, even after cardiac transplantation.RECENT
FINDINGS It has been shown that early metabolic support can improve the
recovery of the ischaemic heart. This paper reviews recent findings on
substrates that can support the failing myocardium, which are mainly
glucose-insulin, glutamine, taurine, selenium, thiamine, folic acid, and omega-3
fatty acids. Ischaemia-reperfusion generates tissue lesions that can be partly
prevented through substrate manipulation.SUMMARY Shifting the substrate
metabolism from lipids to carbohydrates and reinforcing the antioxidant status
reduces the deleterious biological and clinical consequences of acute ischaemic
events. The use of the glucose-insulin-potassium infusion has become widespread
with the re-discovery of its value in modulating cellular metabolism and
accelerating recovery of the ischaemic myocardium. Antioxidants have gained
acceptance in the perioperative phase, as well as in chronic heart failure. This
constitutes another piece of evidence in favour of early metabolic and
nutritional intervention. There also appears to be room for the prevention of
acute deterioration of cardiac function after surgery with the preoperative
administration of oral supplements containing omega-3 fatty acids. PMID: 8681458 [PubMed - indexed for MEDLINE]"medlineCarbohydrate-binding proteins in cancer, and their ligands as
therapeutic agents.Experimental evidence directly implicates complex carbohydrates in
recognition processes, including adhesion between cells, adhesion of cells to
the extracellular matrix, and specific recognition of cells by one another. In
addition, carbohydrates are recognized as differentiation markers and as
antigenic determinants. Lectins are nonenzymatic proteins present in plants
and animals, which preferentially bind to specific carbohydrate structures
and play an important role in cell recognition. Modified carbohydrates and
oligosaccharides have the ability to interfere with carbohydrate-protein
interactions and therefore, inhibit the cell-cell recognition and adhesion
processes, which play an important role in cancer growth and progression.
Carbohydrate ligands therefore, are candidates to play important roles in
cancer therapeutics."
1: Cancer Lett 1999 Jul 19;142(1):91-6

Li D, Yee JA, Thompson LU, Yan L. Department of Biomedical Sciences, Creighton University
School of Medicine, Omaha, NE
68124-0405, USA. We investigated the effect of dietary supplementation
with secoisolariciresinol diglycoside (SDG),
a lignan precursor isolated from flaxseed, on
experimental metastasis of B16BL6 murine
melanoma cells in C57BL/6 mice. Four diets were
compared: a basal diet (control group) and
the basal diet supplemented with SDG at 73, 147 or 293
micromol/kg (equivalent to SDG
provided in the 2.5, 5 or 10% flaxseed diet). Mice were
fed the diet for 2 weeks before and after
an intravenous injection of 0.6 x 10(5) tumor cells. At
necropsy, the number and size of tumors
that formed in the lungs were determined. The median
number of tumors in the control group was
62, and those in the SDG-supplemented groups were 38, 36
and 29, respectively. The last was
significantly different from the control (P < 0.01). Dietary supplementation with SDG at 73, 147
and 293 micromol/kg also decreased tumor size (tumor
cross-sectional area and volume) in a
dose-dependent manner compared with the control values.
These results show that SDG
reduced pulmonary metastasis of melanoma cells and
inhibited the growth of metastatic tumors
that formed in the lungs. It is concluded that dietary
supplementation with SDG reduces
experimental metastasis of melanoma cells in mice. PMID: 10424786 [PubMed - indexed forflaxseed melanoma-medline MEDLINE] "Protective effects of dietary phytoestrogens in chronic renal disease.1: J Ren Nutr 2001 Oct;11(4):183-93
Protective effects of dietary phytoestrogens in chronic renal disease.
Ranich T, Bhathena SJ, Velasquez MT.
Division of Renal Diseases and Hypertension, Department of Medicine, George Washington
University Medical Center, Washington, DC 20037, USA.
Phytoestrogens are naturally occuring plant compounds that are present primarily in soybeans as
isoflavones and in flaxseed as lignans. Because of their structural similarity to endogenous
estrogens, phytoestrogens bind to both estrogen receptors (ER)-alpha and beta (but more
strongly to ER-beta) and exert estrogen-like effects. There is increasing evidence that dietary
phytoestrogens have a beneficial role in chronic renal disease. Nutritional intervention studies
have shown that consumption of soy-based protein and flaxseed reduces proteinuria and
attenuates renal functional or structural damage in animals and humans with various forms of
chronic renal disease. It is not clear which component(s) of the soybean or flaxseed is (are)
responsible for the protective effects observed in experimental animals and in limited studies in
humans. Vegetable protein has been shown to have a beneficial effect on renal disease in animals
and humans. Thus, the role of soy and flaxseed cannot be ruled out. Isoflavones and lignans are
readily absorbed from the gut and converted to active metabolites, which may be partly
responsible for the beneficial renal effects of soy protein and flaxseed. In addition, an interaction
between type of protein and phytoestrogens is also possible. The biological actions of isoflavones
and lignans have been well defined in different cell types in vitro and also in vivo, but how these
compounds might reduce renal injury remains to be elucidated. Possible mechanisms include
inhibition of cell growth and proliferation via ER-mediated mechanisms or non-ER-mediated
pathways through inhibition of tyrosine protein kinases, modulation of growth factors involved in
extracellular matrix synthesis and fibrogenesis, inhibition of cytokine-induced activation of
transcription factors, inhibition of angiogenesis, antioxidative action, suppression of platelet
activating factor and platelet aggregation, and immunomodulatory activity. To date, clinical trials
in humans are few, of relatively short duration, and involve a small number of patients.
Prospective randomized trials are needed to evaluate the long-term safety and effectiveness of
dietary phytoestrogens on renal disease progression in patients with chronic renal failure.
Copyright 2001 by the National Kidney Foundation, Inc.

FLAXSEED LIGNANS & THE IMMUNE SYSTEM -a great review"
Flaxseed contains Secoisolariciresinol diglucoside (SDG), a potent antioxidant and a known precursor of the mammalian lignans,
enterolactone and enterodiol. These compounds have other pharmacological properties including phytoestrogen properties similar to
isoflavones. Studies performed in the Department of Physiology, College of Medicine, University of Saskatchewan, have shown that
SDG prevents the development of hypercholesterolemic atherosclerosis, reduces total cholesterol and LDL-cholesterol,
and has a tendency to raise HDL-cholesterol in animal models. In addition, SDG has shown the ability to lower blood
pressure, and has demonstrated that it is effective in preventing diabetes mellitus (Type I and Type II) and endotoxic
shock. ""The rapid rate of postmenopausal bone loss is mediated by the inflammatory cytokines interleukin-1, interleukin-6, and tumor
necrosis factor alpha. Dietary supplementation with flaxseeds and flaxseed oil in animals and healthy humans significantly
reduces cytokine production while concomitantly increasing calcium absorption, bone calcium, and bone density. Possibilities may
exist for the therapeutic use of the omega-3 fatty acids, as supplements or in the diet, to blunt the increase of the
inflammatory bone resorbing cytokines produced in the early postmenopausal years, in order to slow the rapid rate of
postmenopausal bone loss. Evidence also points to the possible benefit of gamma-linolenic acid in preserving bone density.
(Kettler D, Altern Med Rev, 6(1): 61, 2001) ""Results of many studies indicate that consumption of n-3 fatty acids can benefit persons with cardiovascular disease and
rheumatoid arthritis. However, encapsulated fish oil is unlikely to be suited to lifetime daily use and recommendations to increase
fish intake have not been effective. Foods naturally rich in n-3 fatty acids, such as flaxseed meal can be used to achieve desired
biochemical effects without the ingestion of supplements or a change in dietary habits. A wide range of n-3-enriched foods could be
developed on the basis of the therapeutic and disease-preventive effects of n-3 fatty acids. (Mantzioris E, et al, Am J Clin Nutr, 72(1):
42, 2000) "
Am J Clin Nutr 2002 Dec;76(6):1191-201
:
Beneficial role of dietary phytoestrogens in obesity and diabetes.
Bhathena SJ, Velasquez MT.
Phytonutrients Laboratory, Beltsville Human Nutrition Research Center,
Agricultural Research Service, US Department of Agriculture, Beltsville, MD
20705, USA. bhathens@ba.ars.usda.govEvidence is emerging that dietary phytoestrogens play a beneficial role in
obesity and diabetes. Nutritional intervention studies performed in animals and
humans suggest that the ingestion of soy protein associated with isoflavones and
flaxseed rich in lignans improves glucose control and insulin resistance. In
animal models of obesity and diabetes, soy protein has been shown to reduce
serum insulin and insulin resistance. In studies of human subjects with or
without diabetes, soy protein also appears to moderate hyperglycemia and
reduce body weight, hyperlipidemia, and hyperinsulinemia, supporting its
beneficial effects on obesity and diabetes. However, most of these clinical
trials were relatively short and involved a small number of patients.
Furthermore, it is not clear whether the beneficial effects of soy protein and
flaxseed are due to isoflavones (daidzein and genistein), lignans (matairesinol
and secoisolariciresinol), or some other component. Isoflavones and lignans
appear to act through various mechanisms that modulate pancreatic insulin
secretion or through antioxidative actions. They may also act via estrogen
receptor-mediated mechanisms. Some of these actions have been shown in vitro,
but the relevance of these studies to in vivo disease is not known. The diversity
of cellular actions of isoflavones and lignans supports their possible beneficial
effects on various chronic diseases. Further investigations are needed to
evaluate the long-term effects of phytoestrogens on obesity and diabetes
mellitus and their associated possible complications.
Sulfur in human nutrition and applications in medicine.Because the role of elemental sulfur in human nutrition has not been studied extensively, it is the
purpose of this article to emphasize the importance of this element in humans and discuss the
therapeutic applications of sulfur compounds in medicine. Sulfur is the sixth most abundant
macromineral in breast milk and the third most abundant mineral based on percentage of total body
weight. The sulfur-containing amino acids (SAAs) are methionine, cysteine, cystine, homocysteine,
homocystine, and taurine. Dietary SAA analysis and protein supplementation may be indicated for
vegan athletes, children, or patients with HIV, because of an increased risk for SAA deficiency in
these groups. Methylsulfonylmethane (MSM), a volatile component in the sulfur cycle, is another
source of sulfur found in the human diet. Increases in serum sulfate may explain some of the
therapeutic effects of MSM, DMSO, and glucosamine sulfate. Organic sulfur, as SAAs, can be
used to increase synthesis of S-adenosylmethionine (SAMe), glutathione (GSH), taurine, and
N-acetylcysteine (NAC). MSM may be effective for the treatment of allergy, pain syndromes,
athletic injuries, and bladder disorders.Other sulfur compounds such as SAMe, dimethylsulfoxide
(DMSO), taurine, glucosamine or chondroitin sulfate, and reduced glutathione may also have clinical
applications in the treatment of a number of conditions such as depression, fibromyalgia, arthritis,
interstitial cystitis, athletic injuries, congestive heart failure, diabetes, cancer, and AIDS. Dosages,
mechanisms of action, and rationales for use are discussed. The low toxicological profiles of these
sulfur compounds, combined with promising therapeutic effects, warrant continued human clinical
trails.
Sulfur amino acid deficiency depresses brain glutathione concentration.Dietary sulfur amino acid content is a major determinant of glutathione concentration in some
tissues. We examined whether brain glutathione (GSH), a key component of antioxidant defense
important for minimizing ischemic injury, was also responsive to short-term sulfur amino acid
deficiency. Female Long-Evans adult rats were fed a sulfur-deficient L-amino acid defined diet for
five days; the control diet was supplemented with L-cystine and L-methionine (n = 6). Sulfur amino
acid deficiency was confirmed by a reduction in liver cysteine and GSH concentrations, marked
decreases in food intake, and weight loss. GSH concentration analyzed by reverse-phase high
performance liquid chromatography was significantly depressed in the neocortex and thalamus of
deficient rats. Brain cysteine was not decreased in a parallel manner. Classical glutathione
peroxidase activity was increased in the liver and brain of sulfur amino acid deficient rats. This
suggests an upregulation of antioxidant defense but these findings may be complicated by
alterations in tissue composition. The depletion of brain GSH by a reduced supply of dietary
precursors may be important during brain ischemia when the rate of GSH utilization and the need
for synthesis are increased.Effects of dietary polyunsaturated fatty acid supplementation in early renal
insufficiency in dogs.Dietary supplementation with polyunsaturated fatty acids (PUFAs) alters the course of
experimental kidney disease in dogs. In particular, supplementation with omega-6 PUFAs
hastens the decline of kidney function, and omega-3 PUFAs are renoprotective. We investigated
the early stages of renal insufficiency to determine whether PUFA supplementation altered the
magnitude of hypercholesterolemia or glomerular hemodynamics. Two months after 11/12
nephrectomy, dogs were randomly divided into three groups of 6 animals each. Each group of
dogs was then fed a low-fat basal diet supplemented with one of three sources of lipid to achieve
a final concentration of 15% added fat. Fat sources were rich in omega-3 PUFAs (menhaden fish
oil, group FO), omega-6 PUFAs (safflower oil, group SO), or saturated fatty acids (beef tallow,
group C). Early in renal insufficiency, before significant kidney damage, group FO had a lower
(PWhey protein concentrate (WPC) and glutathione modulation in cancer
treatment.The glutathione (GSH) antioxidant system is foremost among the cellular protective mechanisms.
Depletion of this small molecule is a common consequence of increased formation of reactive
oxygen species during increased cellular activities. This phenomenon can occur in the lymphocytes
during the development of the immune response and in the muscular cells during strenuous
exercise. It is not surprising that so much research has been done, and is still being done on this
small tripeptide molecule. Whey protein concentrate has been shown to represent an effective and
safe cysteine donor for GSH replenishment during GSH depletion in immune deficiency states.
Cysteine is the crucial limiting amino acid for intracellular GSH synthesis. Animal experiments
showed that the concentrates of whey proteins also exhibit anti-carcinogenesis and anticancer
activity. They do this via their effect on increasing GSH concentration in relevant tissues, and may
have anti-tumor effect on low volume of tumor via stimulation of immunity through the GSH
pathway. It is considered that oxygen radical generation is frequently a critical step in
carcinogenesis, hence the effect of GSH on free radicals as well as carcinogen detoxification, could
be important in inhibiting carcinogenesis induced by a number of different mechanisms. Case
reports are presented which strongly suggest an anti-tumor effect of a whey protein dietary
supplement in some urogenital cancers. This non toxic dietary intervention, which is not based on
the principles of current cancer chemotherapy, will hopefully attract the attention of laboratory and
clinical oncologists.
" TARGET="_blank" >Fat soluable vitamins A,D,E,K

Friday April 13 06:39 PM EDT
Study: Common Seed Fights Cancer
A recent Canadian study shows that a common seed may be a promising new cancer
fighter, researchers say.
Dr. Paul Gross of Princess Margaret Hospital and a team of
researchers from the University of
Toronto asked a group of newly diagnosed breast cancer
patients to eat two tablespoons of ground
flaxseed in a muffin each day. Then, Gross' research team
analyzed samples of their tumors.
The study found that flax actually slowed the growth of
breast cancer.
"The scientific community is very interested in this
study," Gross said. "We've been bombarded by
other investigators from around the world."
Researchers found that in less than a month, the women
taking flaxseed slowed their rate of tumor
growth by up to 33 percent. There also was nearly a
60-percent drop in the spread of the most
aggressive cancer cells.
"Flaxseed is the first nutritional product that has been studied, and that has
produced hard scientific evidence," Gross said.
According to the study, researchers believe that a fiber in the seed helps to
sweep the hormone estrogen out of the body, which
blocks its ability to make tumors grow.
Flax would be the first cancer treatment that isn't a chemical, researchers
said. However, since flax is a food, it doesn't have the
backing of a drug company. Researchers said that they don't know how much
longer they would be able to continue their
work.
Some cancer support groups believe that the data shouldn't be ignored.
"There is a community out there who are hungry for this kind of information,
and it won't bother them that it's not a
pharmaceutical," Sue Wright of the Willow Breast Cancer Support Center. "In
fact, it might even encourage them."

Studies on Fish Oil which make one wonder about possible drawbacks-

J Nutr. 2003 Apr;133(4):999-1003. :
IRP1 activity and expression are increased in the liver and the spleen of rats fed fish oil-rich diets and are related to oxidative stress.
Miret S, McKie AT, Saiz MP, Bomford A, Mitjavila MT.
Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Spain.
Many clinical studies have indicated that diets rich in fish oil (FO) reduce the risk of cardiovascular disease and have anti-inflammatory and antithrombotic properties. Although the therapeutic effects of FO have been well described, their impact on iron metabolism remains unclear. The aim of this work was to study the activity and expression of IRP1 in the liver and the spleen of rats fed FO-rich diets with 0 (FO-0) or 100 (FO-1) mg/kg of all-rac-alpha-tocopherol acetate. We also measured nonheme iron, alpha-tocopherol and retinol concentrations, and superoxide (SOD) and catalase activity in these organs. Rats fed FO were compared to rats fed a corn oil (CO)-rich diet with 100 mg/kg all-rac-alpha-tocopherol acetate. The activity and expression of IRP1 in both the liver and the spleen of rats fed FO diets were greater than in those fed the CO diet. FO-fed rats also had lower nonheme iron concentrations in these organs. Hepatic alpha-tocopherol and retinol concentrations and SOD activity were lower in FO-0-fed rats compared to those fed the CO diet. In the spleen, alpha-tocopherol and retinal concentrations were not altered but SOD activity was lower in FO-0- fed rats, whereas catalase activity was greater than in rats fed CO. The results indicate that there is an increase in oxidative stress in the liver and in the spleen of rats fed FO diets. These changes, together with the reduction of nonheme iron concentrations in both FO-0- and FO-1-fed rats, may explain the increase in activity and expression of IRP1. Therefore, the ingestion of FO-rich diets should be monitored under close supervision.

Br J Nutr. 2003 Jan;89(1):11-8. :
Effects of fish oil- and olive oil-rich diets on iron metabolism and oxidative stress in the rat.
Miret S, Saiz MP, Mitjavila MT.
Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal, 645, Spain.The objective of the present study was to examine the effects of fish oil (FO)- and olive oil (OO)-rich diets on Fe metabolism and oxidative stress. Rats were fed for 16 weeks with diets containing 50 g lipids/kg; either OO, maize oil (MO) or FO. OO or MO diets contained a standard amount (100 mg/kg) of all-rac-alpha-tocopheryl acetate. FO diets were supplemented with 0, 100 or 200 mg all-rac-alpha-tocopheryl acetate/kg (FO-0, FO-1 or FO-2 diets, respectively). At the end of the feeding period, we measured non-haem Fe stores in liver and spleen, and erythrocyte and reticulocyte count. We also determined antioxidants and products derived from lipid peroxidation in plasma and erythrocytes. Our results showed reduced non-haem Fe stores in rats fed any of the FO diets. Reticulocyte percentage was higher in the rats fed FO-0 and FO-1. Plasma alpha-tocopherol was very low in rats fed the FO-0 diet. Rats fed the FO-1 and FO-2 diets showed higher alpha-tocopherol in plasma than the FO-0 group but lower than the MO or OO groups. We did not observe such differences in the alpha-tocopherol content in erythrocyte membranes. Superoxide dismutase and glutathione peroxidase activities were lower in the erythrocytes of rats fed the FO-0 diet. The products derived from lipid peroxidation were also higher in the FO groups. The administration of FO-rich diets increased lipid peroxidation and affected Fe metabolism. On the other hand, the OO-rich diet did not increase oxidative stress and did not alter Fe metabolism. Based on these results, we conclude that FO supplementation should be advised carefully.

Oxidative Stress

Br J Dermatol. 2003 May;148(5):913-22. :
Oxidative stress in malignant melanoma and non-melanoma skin cancer.
Sander CS, Hamm F, Elsner P, Thiele JJ.
Department of Dermatology, Friedrich Schiller University Jena, Erfurter Strasse 35, D-07740 Jena, Germany.
Background Solar ultraviolet (UV) radiation is considered to be a major aetiological factor in melanoma and non-melanoma skin cancer. A growing body of evidence indicates that oxidative stress is involved in photocarcinogenesis. However, in vivo data for human skin are still lacking. Reactive oxygen species participate in a number of pathophysiological processes including DNA damage and lipid peroxidation (LPO) and are considered to be a key factor in tumour progression. Objectives We hypothesized that in human skin cancer the natural redox balance is disturbed and that this imbalance may result in an accumulation of LPO products. Methods To test this, skin biopsies of superficial spreading melanoma were compared with age-matched benign melanocytic naevi and young healthy controls. Additionally, non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma) and actinic keratosis were investigated (n = 18 each). Expression of the antioxidant enzymes, copper-zinc superoxide dismutase, manganese superoxide dismutase and catalase was analysed by immunohistochemical techniques. To detect LPO products, protein-bound malondialdehyde (MDA) was visualized. Results In human melanoma biopsies, a significant overexpression of the antioxidant enzymes was found when compared with surrounding non-tumour tissue, benign melanocytic naevi, and young controls. Intriguingly, the LPO marker MDA was significantly increased in melanoma tissue. MDA was located not only in typical melanoma cells, but also occurred in surrounding keratinocytes. In contrast, a severely disturbed antioxidant balance with diminished antioxidant enzymes was found in non-melanoma tumours, whereas MDA was elevated only in squamous cell carcinomas. Conclusions These findings indicate that oxidative stress may play different roles in the pathogenesis of human skin cancers. In non-melanoma skin cancer, a diminished antioxidant defence caused by chronic UV exposure might contribute to multistep carcinogenesis, whereas melanoma cells exhibit increased oxidative stress which could damage surrounding tissue and thus support the progression of metastasis.: Eur J Med Chem. 2003 May;38(5):451-7.:
The association of vitamins C and K(3) kills cancer cells mainly by autoschizis, a novel form of cell death. Basis for their potential use as coadjuvants in anticancer therapy.
Verrax J, Cadrobbi J, Delvaux M, Jamison JM, Gilloteaux J, Summers JL, Taper HS, Buc Calderon P.
Unite de Pharmacocinetique, Metabolisme, Nutrition et Toxicologie, Departement des sciences pharmaceutiques, Universite Catholique de Louvain, Bruxelles, Belgium
Deficiency of alkaline and acid DNase is a hallmark in all non-necrotic cancer cells in animals and humans. These enzymes are reactivated at early stages of cancer cell death by vitamin C (acid DNase) and vitamin K(3) (alkaline DNase). Moreover, the coadministration of these vitamins (in a ratio of 100:1, for C and K(3), respectively) produced selective cancer cell death. Detailed morphological studies indicated that cell death is produced mainly by autoschizis, a new type of cancer cell death. Several mechanisms are involved in such a cell death induced by CK(3), they included: formation of H(2)O(2) during vitamins redox cycling, oxidative stress, DNA fragmentation, no caspase-3 activation, and cell membrane injury with progressive loss of organelle-free cytoplasm. Changes in the phosphorylation level of some critical proteins leading to inactivation of NF-kappaB appear as main intracellular signal transduction pathways. The increase knowledge in the mechanisms underlying cancer cells death by CK(3) may ameliorate the techniques of their in vivo administration. The aim is to prepare the introduction of the association of vitamins C and K(3) into human clinics as a new, non-toxic adjuvant cancer therapy.
FASEB J. 2003 May 20 [Epub ahead of print]. :
Tetracycline-dependent regulation of formamidopyrimidine DNA glycosylase in transgenic mice conditionally reduces oxidative DNA damage in vivo.
Laposa RR, Henderson JT, Wells PG.
8-Oxo-deoxyguanosine (8-oxo-dG) is a pervasive oxidative DNA lesion formed by endogenous oxidative stress and enhanced by drugs and environmental chemicals. This lesion results in transcriptional errors and mutations and is linked to neurodegeneration, teratogenesis, cancer, and other pathologies. We demonstrate that the neonatal central nervous system of transgenic mice carrying the tetracycline-regulable DNA repair gene formamidopyrimidine DNA glycosylase (fpg) has a 50% reduction in 8-oxo-dG levels. This enhanced DNA repair is suppressed by treatment with doxycycline. For the first time, this murine model permits the level of a specific DNA oxidation product to be regulated in a temporally and spatially specific manner, allowing its role as a primary or secondary factor in neurodegenerative disease to be determined in vivo.
Free Radic Biol Med. 2003 Jun 1;34(11):1369-82. :
Oxidative stress and calcium signaling in the adverse effects of environmental particles (PM(10)).
Donaldson K, Stone V, Borm PJ, Jimenez LA, Gilmour PS, Schins RP, Knaapen AM, Rahman I, Faux SP, Brown DM, MacNee W.
Colt/ELEGI Laboratories, Centre for Inflammation Research, The University of Edinburgh Medical School, Edinburgh, UK
This review focuses on the potential role that oxidative stress plays in the adverse effects of PM(10). The central hypothesis is that the ability of PM(10) to cause oxidative stress underlies the association between increased exposure to PM(10) and both exacerbations of lung disease and lung cancer. Pulmonary inflammation may also underlie the cardiovascular effects seen following increased PM(10), although the mechanisms of the cardiovascular effects of PM(10) are not well understood. PM(10) is a complex mix of various particle types and several of the components of PM(10) are likely to be involved in the induction of oxidative stress. The most likely of these are transition metals, ultrafine particle surfaces, and organic compounds. In support of this hypothesis, oxidative stress arising from PM(10) has been shown to activate a number of redox-responsive signaling pathways in lung target cells. These pathways are involved in expression of genes that play a role in responses relevant to inflammation and pathological change, including MAPKs, NF-kappaB, AP-1, and histone acetylation. Oxidative stress from particles is also likely to play an important role in the carcinogenic effects associated with PM(10) and hydroxyl radicals from PM(10) cause DNA damage in vitro.J Toxicol Environ Health A. 2003 Mar 14;66(5):411-5. :
Glutathione and glutathione-related enzymes in colorectal cancer patients.
Saygili EI, Akcay T, Konukoglu D, Papilla C.
Department of Biochemistry, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey. ilksaygili@mynet.com
In recent years much attention has been focused on the role of glutathione (GSH) and GSH-related enzymes such as glutathione peroxidase (GSH Px), glutathione reductase (GSH Red), and glutathione S-transferase (GST) in the inhibition of free radical-induced carcinogenesis. In this study, erythrocyte GSH levels and activities of GSH Px, GSH Red, and GST were determined in patients with colorectal tumors (n = 20, mean age 54.5 +/- 8.3 yr). Erythrocyte GSH Red and GST activities were significantly higher in patients with colorectal tumors. Erythrocyte GSH levels and GSH Px activities were found to be significantly decreased in the patients. When the patients were classified based on their clinical grading (Dukes classifications), there was no significant difference in studied parameters between Dukes B and Dukes C. Our results suggest that oxidative stress may play an important role in colorectal tumorigenesis and that these events have no effect on the clinical grading of the colorectal tumor.
Biochim Biophys Acta. 2003 Apr 11;1647(1-2):127-30. :
Antitumor effect of vitamin B6 and its mechanisms.
Komatsu S, Yanaka N, Matsubara K, Kato N.
Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
Epidemiological studies have reported an inverse association between vitamin B(6) intake and colon cancer risk. Our recent study has been conducted to examine the effect of dietary vitamin B(6) on colon tumorigenesis in mice. Mice were fed diets containing 1, 7, 14 or 36 mg/kg pyridoxine for 22 weeks, and given a weekly injection of azoxymethane (AOM) for the initial 10 weeks. Compared with the 1 mg/kg pyridoxine diet, 7, 14 and 35 mg/kg pyridoxine diets significantly suppressed the incidence and number of colon tumors, colon cell proliferation and expressions of c-myc and c-fos proteins. Supplemental vitamin B(6) lowered the levels of colonic 8-hydroxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE, oxidative stress markers) and inducible nitric oxide (NO) synthase protein. In an ex vivo serum-free matrix culture model using rat aortic ring, supplemental pyridoxine and pyridoxal 5'-phosphate (PLP) had antiangiogenic effect. The results suggest that dietary vitamin B(6) suppresses colon tumorigenesis by reducing cell proliferation, oxidative stress, NO production and angiogenesis.
Curr Med Chem. 2003 Jun;10(12):1021-34. :
The role of iron chelation in cancer therapy.
Buss JL, Torti FM, Torti SV.
Drug Discovery Chemistry, Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, CH-4123 Allschwil / BL, Switzerland. christoph.boss@actelion.com and christoph.binkert@actelion.com
This review focuses on advances and strategies in the use of iron chelators as anti-tumor therapies. Although the development of iron chelators for human disease has focused primarily on their use in the treatment of secondary iron overload, chelators may also be useful anti-tumor agents. They can deplete iron or cause oxidative stress in the tumor due to redox perturbations in its environment. Iron chelators have been tested for their anti-tumor activity in cell culture experiments, animal models and human clinical trials. Largely for pragmatic reasons, clinical studies of the anti-tumor activity of iron chelators have generally focused on desferrioxamine (DFO), a drug approved for the treatment of iron overload. These studies have shown that DFO can retard tumor growth in many different experimental contexts. However, the activity of DFO is modest, and advances in the use of chelators as anti-cancer agents will require the development of new chelators based on new paradigms. Examples of iron chelators that have shown promising anti-tumor activity (in various stages of development) include heterocyclic carboxaldehyde thiosemicarbazones, analogs of pyridoxal isonicotinoyl hydrazone, tachpyridine, O-trensox, desferrithiocin, and other natural and synthetic chelators. Apart from their use as single agents, chelators may also synergize with other anti-cancer therapies. The development of chelators as anticancer agents is largely an unexplored field, but one with extraordinary potential to impact human cancer.